Exceptional occurrences have fundamental interest in evolution relevant to understanding adaptations and origins. Monogeneans primarily infect aquatic lower vertebrates, i. e. fish, amphibians and chelonian reptiles, but there is a single instance of colonisation of a mammal: Oculotrema hippopotami Stunkard, 1924 infecting the eye of Hippopotamus amphibius Linnaeus. Its combination of systematic characters is amongst the most diverse in the Polystomatidae Gamble, 1896 and relationships are obscure. This study emphasises the primary significance of two features: the reinforcement of haptoral suckers with an internal skeleton and the pattern of ciliated cells on the oncomiracidium, especially the presence of conjoined cells. Closest relationships are with polystomatids infecting chelonians, specifically species of Polystomoides Ward, 1917 from the oral cavity/pharynx, or more likely (but with currently incomplete evidence) species of Neopolystoma Price, 1939 from the eye. Morphological characters of polystomoidines, all of which infect chelonians, appear to have remained relatively stable since at least the Jurassic (from zoogeographical evidence), but the highly derived characters of species of Oculotrema may have evolved during the comparatively short period (16 million years) since the Miocene origin of Hippopotaminae Gray. However, the initial host switch may plausibly have been to hippo ancestors, the anthracotheres, with similar semi-aquatic ecology and an Eocene origin (41 million years ago). Over the same time-scale, the oncomiracidial cell pattern remained closely comparable with that of presumed ancestors, emphasising its value in phylogenetic analyses.